Réaction #43772

Équation de réaction

(S)-2-bromophenylalanine

K2CO3

→

(S)-2,3-dihydro-1H-indole-2-carboxylic acid

Rendement 49.5%

Solvants

NMP

Conditions de réaction

Traitement

1. 1
   AutreThe reactor was flushed with argon
2. 2
   TempératureThe reaction mixture was cooled to 25° C.
3. 3
   workup.ADDITION40 mL H2O and 50 mL aqueous EtOAc were added
4. 4
   AutreThe phases were separated
5. 5
   ExtractionThe H2O phase was extracted with 2×50 mL aqueous EtOAc
6. 6
   LavageThe combined organic layers were washed with 25 mL
7. 7
   ConcentrationThen the organic phase was concentrated
8. 8
   workup.DISSOLUTIONThe residue was dissolved in 16 mL 5N HCl

Mode opératoire

A flask was charged successively with 9.76 g (40.0 mmol) (S)-2-bromophenylalanine, 5.80 g (42.0 mmol) K2CO3, 40 mg (0.4 mmol) CuCl and 40 g NMP. The reactor was flushed with argon and then kept under a slow stream of argon. The reaction mixture was stirred and heated until 80° C. and kept at this temperature. Samples were taken regularly and analyzed by HPLC. After 3.5 h full conversion of (S)-2-bromophenylalanine was found. The reaction mixture was cooled to 25° C. and then 40 mL H2O and 50 mL aqueous EtOAc were added. The pH of this mixture was adjusted to 3.3 with 3.5 g 37% aqueous HCl. The phases were separated. The H2O phase was extracted with 2×50 mL aqueous EtOAc. The combined organic layers were washed with 25 mL sat aqueous NaCl. Then the organic phase was concentrated. The residue was dissolved in 16 mL 5N HCl, followed by pH adjustment to 2.1 with 9.4 g 32% aqueous NaOH. The precipitated (S)-2,3-dihydro-1H-indole-2-carboxylic acid was isolated by filtration and washed with 2×10 mL H2O. 3.24 g (19.8 mmol) (S)-2,3-dihydro-1H-indole-2-carboxylic acid was found after drying. Yield 49.5%, ee>99%.

Source